N-(4-fluorophenyl)-2,3-dichloromaleimide used as a fungicide

ABSTRACT

The compound, N-4(-fluorophenyl)-2,3-dichloromaleimide, has been found to possess good fungicidal properties, particularly for such plant diseases as tomato diseases, rice blight, anthracnose disease in cucumbers and black spot disease in citrus fruit. This compound can be effectively used in lower concentrations compared with previously known fungicidal maleimides.

United States Patent [191 Kawada et al.

[ 1 N-(4-FLUOROPHENYL)2,3-

DICHLOROMALEIMIDE USED AS A FUNGICIDE [75] Inventors: Seigo Kawada, Kikukawa; Hideo Ito,

Shimizu; Kazuo Matsui; Hiroshi Kasugai, both of Tokyo, all of Japan [73] Assignee: Mitsubishi Chemical Industries Limited, Tokyo, Japan 22 Filed: Sept. 14,1972

21 Appl.No.:288,936

Related us. Application Data [62] Division of Ser. No. 104,464, Jan. 6, 1971 Pat. No.

[30] Foreign Application Priority Data Jan. 10, 1970 Japan 45-3l43 52 us. Cl. 424/274 [51] Int. Cl A01n 9/22 [58] Field of Search 424/274 [56] References Cited UNITED STATES PATENTS 2,962,504 11/1960 Walker et a1. 260/3265 June 28, 1974 3,018,292 1/1962 Sauers et a1. 260/3265 3,129,225 4/1964 Shapiro et al 260/2472 3,148,196 9/1964 Ladd H 250/3265 FOREIGN PATENTS OR APPLICATIONS 852,634 10/1960 Great Britain OTHER PUBLICATIONS Torgeson et al. Contributions from Boyce Thompson Institute 22 67-70 (1963) Primary Examiner-Albert T. Meyers Assistant Examiner-Leonard ,Schenkman Attorney, Agent, or Firm-Oblon, Fisher, Spivak, Mc- Clelland & Maier 5 7] ABSTRACT The compound, N-4( -fl uorophenyl )-2 ,3- dichloromaleimide, has been found to possess good fungicidal properties, particularly for such plant diseases as tomato diseases, rice blight, anthracnose disease in cucumbers and black spot disease in citrus fruit. This compound can be effectively used in lower concentrations compared with previously known fungicidal maleimides.

5 Claims, N0 Drawings This is a division, of application Ser. No. 104,464, filed Jan. 6, 1971 now US. Pat. No. 3,734,937.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates generally to a novel maleimide composition and to a fungicide containing said maleimide therein as an active ingredient which is effective for protecting agricultural plants from detrimental parasitic microorganisms. More specifically, this invention relates to a fungicide containing N-(4- fluorophenyl)dichloromaleimide as the active ingredient.

2. Description of Prior Art N-(4-methylphenyl)dichloromaleimide, N- cyclohexyl dichloromaleimide and the like are known to possess fungicidal activity and are known to be effective against various plant detriments. See, for instance, Japanese Patent Publication No. 12798/1960 by Tenis and Lee. However, those dichloromaleimides have proven to be at least partially unsatisfactory for many plant applications.

For example, N-cyclohexyl dichloromaleimide has proven to be ineffective against rice blight, anthrax disease in cucumbers and black spot disease in citrus fruits at a concentration level of 500 ppm. Likewise, the fungicidal activity of N-(4-methylphenyl) dichloromaleimide is tremendously reduced at lower concentrations and is almost negligible against anthracnose disease in cucumbers and black spot disease of citrus fruits.

A need exists therefore for a fungicidal composition which can exert fungicidal activity at lower concentration levels than required for the previously known maleimide compounds, and which is effective against a variety of plant detriments.

SUMMARY THE INVENTION Accordingly, it is an object of this invention to provide the new compound N-(4-fluorophenyl)-2,3- dichloromaleimide.

It is another object of this invention to provide a fungicidal compound which is effective at lower concentrations.

Another object of this invention is to provide a fungicidal compound which can be used against a wide variety of plant detriments, and particularly rice blight, anthracnose disease in cucumbers, black spot disease in citrus fruits and tomato disease.

These and other objects have now been attained by the discovery that the said N-(4-fluorophenyl)dichloromaleimide is prominently superior to N-(4- methylphenyl)dichloromaleimide and N-cyclohexyl dichloromaleimide with respect to the fungicidal activity.

DETAILED DESCRIPTION OF THE INVENTION N-(4-fluorophenyl)dichloromaleimide. melts at 245-246C. and can be prepared by reacting, for example, 4-fluoroaniline with dichloromaleic acid, dichloromaleic acid anhydride or an ester thereof.

Dichloromaleic acid, its corresponding anhydride or ester can be prepared by various methods. For example, dichloromaleic acid can be obtained by oxidizing 3-formyl-2,3-dichloroacrylic acid with fuming nitric acid (Ber 38, 2588 90). Dichloromaleic anhydride can be obtained by reacting maleic anhydride with chlorine in the presence of iron (U.S.S.R. Pat. No. 43419). The esters of dichloromaleic acid can be readily obtained from dichloromaleiic acid or anhydride, with the corresponding alcohols.

A suitable solvent is preferably employed in the reaction of 4- fluoroaniline with dichloromalcic acid. etc.

Suitable solvents include for instance, the aromatic hydrocarbons, such as benzene. toluene and xylencs; chloroform, carbon tetrachloride and other chlorinated alkanes; acetone, methyl ethyl ketone and other ketones; methanol, ethanol, and other lower alcohols; lower carboxylic acids such as acetic acid; dioxane and the like. Expecially good results are obtainable with acetic acid.

4-fluoroaniline may be used in an equimolar amount based on the dichloromaleic acid, anhydride, or ester, or may be used in an excess such as 2 moles/mole.

The reaction temperature is maintained at 10 200C, preferably at 40 120C, when dichloromaleic acid or itsanhydride is used, whereas the temperatures may be selected within the range of 0 200C., preferably 30 120C, when an ester of dichloromaleic acidis used.

The reaction time is not critical and can be selected over a wide range, for example, 0.1 20 hours; however, the reaction is usually complete within 1 3 hours.

After the reaction has been completed, the reaction mixture is either poured onto water, if the solvent is water-soluble, or. the solvent is removed by distillation at reduced pressure, if the solvent is insoluble in water,

to depositcrystals of the desired product. The thus obtained crude crystals are recrystallized from an organic solvent, such as acetone, to provide N-(4-fluorophenyl)-2,3-dichloromaleimide in good yield.

The desired product of the present invention can also be prepared by dehydrative cyclization of N-(4-fluorophenyl)-2,3-dichloromaleamic acid, thus N-(4-fluorophenyl)-2,3-dichloromalearnic acid is dissolved in one of the above-cited organic solvents and heated at 50 200C, preferably at 60 130C. Again, the period of heating is not especially critical and can be selected over a wide range of from 0.1 20 hours, although 1 3 hours is usually sufficient.

The reaction mixture after completion of the reaction is treated and purified as discussed above.

The starting material in the latter case, namely, N-(4- fluorophenyl)-2,3-dichloromaleamic acid can be prepared by reacting, for example, 3,4-dichloromaleic acid anhydride with 4-fluoroaniline at relatively low temperatures.

The following Examples illustrate the preparation of N-(4-fluorophenyl)2,3-dichloromaleimide which are presented herein for purposes of illustration only and are not intended to be limiting unless otherwise specified.

EXAMPLE I 2,3-dichloromaleic anhydride 16.7 g. (0.1 moles) was dissolved in ml. of glacial acetic acid. A solution of 4-fluoroaniline 11.1 g. (0.1 moles) dissolved in 30 ml. of glacial acetic acid was added dropwise at l525C., with stirring, over a period of 20 minutes. The mixture was warmed to 70 C. and maintained at that temperature for 2 hours while stirring. Upon Calculated for u OgNCl F C 46.18 H 1.55 N 5.39 Cl 27.27% Found C 45.99 H 1.57 N 5.32 Cl 27.34%

EXAMPLE 2 To a mixture of 2,3-dichloromaleic anhydride, 15.1 g. (0.0903 moles) and 4-fiuoroaniline 10.0 g. (0.0901 moles), 80 ml. of glacial acetic acid was added. The resulting solution was heated under reflux for 3 hours and then cooled to l525C. The reaction mixture was poured into 11. of water, and the crystals precipitated out were collected by filtration and rinsed with water to provide 20.2 g. (yield, 86%) of crude N-(4-fluorophenyl)-2,3-dichloromaleimide melting at 238242C. Recrystallization of the crude crystals from acetone provided pale yellow plates melting at 245246C., which were identified as N-(4-fluorophenyl)-2,3- dichloromaleimide by mixed examination using an authentic specimen as obtained in Example 1.

EXAMPLE 3 2,3-dichloromaleic acid 18.5 g. (0.1 moles) was dissolved in 80 ml. of glacial acetic acid. A solution of 11.1 g. (0.1 moles) of 4-fluoroaniline dissolved in 20 ml. of glacial acetic acid was added dropwise with stirring at 20C. over a period of minutes. The reaction mixture was stirred for an additional 3 hours at 7080C. and allowed to cool to l5*25C. The precipitated crystals were collected by filtration, washed with glacial acetic acid to provide crude N-(4-fluorophenyl)-2,3-dichloromaleimide, melting at 238242C., 21.3 g. (in 82% yield). The precipitate was recrystallized twice from acetone which provided pale yellow plates, melting at 245-245.5C. These were identified as the desired product on admixture with an authentic sample of N-(4-fiuorophenyl)-2,3- dichloromaleimide obtained by Example 1.

EXAMPLE 4 2,3-dichloromaleic acid anhydride, 16.7 g. (0.1 moles) was dissolved in 50 ml. of benzene to which a solution of l 1.1 g. (0.1 moles) of 4-fluoroaniline in 20 ml. of benzene was added dropwise with stirring at l5-20C. over a period of 20 minutes. Stirring was continued for an additional 1 hour at l525C., and the crystals formed by precipitation were filtered and rinsed with benzene to provide white crystals, melting at 222225C., which were identified as N-(4-fiuorophenyl)-2,3-dichloromaleamic acid, 26.3 g. (in 95% yield). The elemental analysis of the product is shown below:

Calculated for CwHaOaNClgF C 43.19; H 2.18; N 5.04; C125.50% Found C 42.86; H 2.01; N 4.72; CI 25.10%

To 13.9 g. (0.05 moles) of N-(4-fluorophenyl)-2,3- dichloromaleamic acid obtained above, was added glacial acetic acid and the resulting solution was heated at 80C. for 2 hours and then allowed to cool to l525C. The crystals formed by precipitation were filtered and rinsed with glacial acetic acid to yield 10.8 g. (yield 83%) of crude N-(4-fluorophenyl)-2,3- dichloromaleimide, melting point of 234238C. These crystals were twice recrystallized from acetone to provide pale yellow plates, melting at 244C, which were identified as N-(4-fluorophenyl)-2,3- dichloromaleimide by mixed examination using an authentic sample obtained in Example 1.

EXAMPLE 5 To 16.7 g. (0.1 moles) of 2,3-dichloromaleic acid anhydride was added 100 ml. of methyl alcohol. The mixture was refluxed for 10 hours while gaseous hydrogen chloride was passed through the reactants. Methanol and hydrogen chloride gas were removed by evaporation under reduced pressure and the residue was distilled to provide 17.1 g. of a fraction boiling at l02105C./ 10 mmHg. This fraction was identified as dimethyl 2,3-dichloromaleate (yield 80%).-The thus obtained 2,3-dichloromaleic acid dimethyl ester, 15 g. (0.0705 moles), was dissolved in 50 ml. of glacial acetic acid, to which a solution of 7.82 g. (0.0705 moles) of 4-fluoroaniline in 20 ml. of glacial acetic acid was added dropwise at l525C. with stirring over a period of 20 minutes. The reaction mixture was further stirred for 2 hours at 4060C., and then glacial acetic acid was removed by distillation under reduced pressure to provide crude N-(4-fluorophenyl)-2,3- dichloromaleimide having a melting point of between 230235C. The crude crystals were recrystallized twice from acetone to provide 13.75 g. (yield, of pale yellow plates, melting at 242244C.

No lowering of the melting point was observed when these crystals were admixed with an authentic sample of N-(4-fluorophenyl)-2,3-dichloromaleimide obtained according to the method described in Example 1, and identified as the same compound thereby.

The compound according to the present invention has been proven to exert definite fungicidal activity at relatively low concentration levels compared with other known maleimide compounds. lts antimicrobial spectrum is rather broad, and so it is effective against a variety of plant detriments as indicated in Tables 1 5. Whereas, N-cyclohexyl dichloromaleimide is ineffective against the rice blight, anthracnose disease in cucumbers and black spot disease in citrus fruits at a concentration level of 500 ppm; and N-(4-methylphenyl)dichloromaleimide has very little fungicidal activity at lower concentrations, especially against anthrax disease in cucumbers and black spot disease of citrus fruits, the compound of the present invention exerted a stable effect even at low concentration levels.

In addition, as shown in Table 5, the fungicidal effect of the compound obtained by the present invention when used in plantation yards was found to be stable and persisted for a relatively long period of time compared with similar compounds, which indicates the unique characteristics of the present compound.

The compound of this invention can be used in combination with conventional carriers (diluent), surfactants and the like, and can be used in the form of a powder, or a wettable powder. it can be directly applied by spraying or can be used after suitable dilution.

The carrier refers hereinafter to a carrier for carrying dust and the like. Liquid carriers include solvents or non-solvents for the active ingredient and the present compound can be either dispersed or dissolved. Suitable liquid carriers include water, benzene, kerosene, alcohol, acetone, methylnaphthalene, xylenes, and so on. Suitable surfactants include the non-ionic surfactants such as polyoxyethylene sorbitan monolaurate, etc.; cationic surfactants, such as alkyl dimethylbenzyl ammonium chloride, and higher alcohol sulfates; amphoteric surfactants, such as lauryl amine derivatives, betaine derivatives, dodecyl amino ethyl glycine, etc. The mode of formulation of the fungicide composition of the present invention will be demonstrated by the following examples. Of course, the additive used and the proportion thereof may be varied as desired. All percents are by weight unless otherwise specified.

EXAMPLE 6:

Powder Preparation A mixture comprising 2% of N-(4-fluorophenyl)- dichloromaleimide and 98% of clay and talc was pulverized and the resulting fine powders were used as a fungicide.

EXAMPLE 7:

Wettable Powder Preparation N-(4-fluorophenyl)dichloromaleimide 50%, a mixture of white carbon and diatomaceous earth 46%, sodium alkylbenzene sulfonate 2%,calcium lignin sulfonate 2% were blended and pulverized. The resulting fine powders were suspended in water and used as a fungicide.

EXAMPLE 8:

Wettable Powder Preparation N-(4-fluorophenyl)dichloromaleimide 50%, diatomaceous earth 47%, sodium dodecyl sulfate 1%, and polyvinyl alcohol 2% were blended and pulverized. The resulting fine powders were suspended in water and used as a fungicide.

Compounds of the present invention were compared with relevant reference compounds.

EXAMPLE 9:

Protection Test on Tomato Disease Tomato plants of 5 6 leave age (species: pond de rosa) was sprayed with 30 cc. per stub of a suspension which was prepared by dilution of the wettable powder (Example 7) with water to the specified concentration. 30 days later, a suspension of a pathogenic microorganism cultured on a potato medium which causes infection of the tomato was used to innoculate the plants. lnnoculation was accomplished by spraying. After innoculation, the tomato plants were placed in a humidic chamber at 24C. for 1 day and night, and then removed to a greenhouse. The situation of the disease was examined after 6 days.

TABLE 1 Protection Value Concentration Test Compound 500 250 I25 W PP PP N-(4-fluorophenyl)dichloromalcimide 98.5 98.0 90.4 N-(2-chlorophenyl)dichloromaleimide 88.6 85.2 68.3 N-(4-chlorophenyl)dichloromaleimide 86.7 84.7 33.9 N-(4-nitrophenyl)dichloromaleimide 68.9 400 Lil N-(Z-trifluoromethylphenyl)dichloromaleimide 47.8 3.0 5.5 N-(Ltrifluoromehtylphenyl)dichloromaleimide l 1.9 5.6 7.8 N-(4-methylphenyl)dichloromaleimide 88.0 80.0 61.7 N-cyclohexyldichloromaleimide 10.0 10.2 4 .9 Manganese ethylene biidithiocarbamate 98.2 95.5 89.2 Untrewd Zone 0 0 0 *Proection value was calculated according to the following formula:

Number of diseased cases in the treated zone Number of diseased cases in the untreated zone EXAMPLE 10:

Protection Test Against Rice Blight Rice plants of 5 6 leave age (species: Kinmaze) was sprayed with 30 cc. per pot of the suspension of wettable powder (Example 8) of the present invention; 3 days later, the rice plants were innoculated by spraying with a suspension containing spores of pathogenic microorganism collected from the blighted leaves of diseased rice. The plants were allowed to stand in a humidic chamber at 24C. and the infection situation was examined after 7 days.

TABLE 2 Protection value Concentration Number of infected spots in the untreated zone EXAMPLE 11:

Protection Test Against Anthracnose Disease in Cucumbers No. of slightly diseased leaves N0. of medium No. of heavily X 3 X diseased leaves X 2 diseased leaves number of the infected spots per seed leaves of cucumbers were counted and the protection value computed from the ratio to the number of the infected spots in the untreated zone.

Protection Test Against Citrus Black Spot Disease Potted citrus seedlings (species: ordinary Unshu tangerine) were sprayed with 600 l/ 10 are per pot of the suspension of the wettable powder of the present invention (Example 8), and 2 days latter were innoculated by spraying a spore suspension of a pathogenic citrus b lack spot fungus cultured on decayed tangerine branc:

Protection Value ("It N0. of total leavesX 3 EXAMPLE 13:

Residual Effect Test Against Citrus Black Spot Disease The wettable powder of the present invention (Example 8) was diluted to 1,000 ppm. and amounts corresponding to 600 1 per 10 are. were sprayed onto a yard of 8-year-old Unshu tangerine trees. The fruits after 5, 18, and 21 days were collected in a ratio of 20 per zone, and were spray innoculated with a spore suspension of citrus black spot disease fungus cultured on decayed tangerine branches. They were then allowed to stay in a humidic chamber at 25C. for 2 days, then removed to a greenhouse, and the situation of the disease was examined after 5 days. The plants were subjected to rain for periods of 5 days, 18 days, and 21 days after the spraying of the fungicide. The quantity of rain was measured at 5.3 mm., 18.6 mm. and 96.2 mm., respec-' tively.

TABLE 5 Protection Value after innoculation The effective concentration adopted was 1000 ppm in each case. Protection Value No. of slightly No. of medium No. of heavily diseased diseased diseased fruits X 1 fruitsX 2 fruits X 3 10 N0. of total fruits 3 X 0 hes. The plants were allowed to stay in a humidic chamber at 25C. for 2 days, then removed to a green house. .The situation of the disease was examined after 24 days.

TABLE 4 Protection Value Concentration Test Compound 500 250 125 pp pp p N-(4-fluorophenyl(dichloromaleimide 100 100 100 N-(4 chlorophenyl)dichloromaleimide 85.5 44.0 23.0 N-'(4-nitrophenyl)dichloromaleimide 46.6 8.1 3.5 N-(2-trifluoromethylphenyl)di chloromalcimide 43.1 7.5 2.4 N-(3trifluoromethylphenyUdichloromaleimide 11.1 5.3 14.2 N-(4-methylphenyl)dichloromaleimide 33.3 25.3 N-cyclohexyldichloromaleimide 10.0 6.4 N-tetrachloroethylthiotetrahydrophthalimide 100 95.0

1. A fungidical composition consisting essentially of a fungicidally effective amount of N-(4-fluorophenyl)- 2.3-diqhlerqma ei md an n iner ee s 2. A method of combatting fungal diseases on plants which comprises applying a fungicidally effective amount of N-(4-fluorophenyl)-2,3-dichloromaleimide to 55 191299121-.-

3. The method of claim 2 wherein the disease is rice b i ht...

4. The method of claim 2 wherein the disease is an- Lracnoseediseaseeof cuctnnber...-.

5. The method of claim 2 wherein the disease is black spot disease of citrus fruit.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent 3 ,821,395 Dated June 28, 1974 Inventor(s) Seigo Kawada, Hideo Ito, Kazuo Matsui and Hiroshi Kasugai It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Page 1, Column 1, line 6, after 'assignors", delete "Mitsubishi Chemical Industries limited, Tokyo, Japan" and insert therefor --of 50% undivided interest each to Mitsubishi Chemical Industries Limited, Tokyo, Japan and Kumiai Chemical Industry Company Limited, Tokyo, Japan--.

Signed and sealed this 1 3th day of March 1.975.

(SEAL) Attest: C. MARSHALL DANN RUTH C. MASON Commissioner of Patents Attesting O ficer and Trademarks FORM P0 1050 (10-69) USCOMM-DC 5O376fP69 .5. GOVERNMENT PRINTING OFFICE: "I, O-flib-lfl 

2. A method of combatting fungal diseases on plants which comprises applying a fungicidally effective amount of N-(4-fluorophenyl)-2,3-dichloromaleimide to said plants.
 3. The method of claim 2 wherein the disease is rice blight.
 4. The method of claim 2 wherein the disease is anthracnose disease of cucumber.
 5. The method of claim 2 wherein the disease is black spot disease of citrus fruit. 